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- W2156421803 abstract "Apoptotic cells are swiftly engulfed by phagocytes and degraded inside phagosomes. Phagosome maturation requires phosphatidylinositol 3-phosphate [PtdIns(3)P], yet how PtdIns(3)P triggers phagosome maturation remains largely unknown. Through a genome-wide PtdIns(3)P effector screen in the nematode Caenorhabditis elegans, we identified LST-4/SNX9, SNX-1, and SNX-6, three BAR domain-containing sorting nexins, that act in two parallel pathways to drive PtdIns(3)P-mediated degradation of apoptotic cells. We found that these proteins were enriched on phagosomal surfaces through association with PtdIns(3)P and through specific protein–protein interaction, and they promoted the fusion of early endosomes and lysosomes to phagosomes, events essential for phagosome maturation. Specifically, LST-4 interacts with DYN-1 (dynamin), an essential phagosome maturation initiator, to strengthen DYN-1’s association to phagosomal surfaces, and facilitates the maintenance of the RAB-7 GTPase on phagosomal surfaces. Furthermore, both LST-4 and SNX-1 promote the extension of phagosomal tubules to facilitate the docking and fusion of intracellular vesicles. Our findings identify the critical and differential functions of two groups of sorting nexins in phagosome maturation and reveal a signaling cascade initiated by phagocytic receptor CED-1, mediated by PtdIns(3)P, and executed through these sorting nexins to degrade apoptotic cells." @default.
- W2156421803 created "2016-06-24" @default.
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- W2156421803 creator A5068665250 @default.
- W2156421803 date "2011-02-01" @default.
- W2156421803 modified "2023-10-15" @default.
- W2156421803 title "Three sorting nexins drive the degradation of apoptotic cells in response to PtdIns(3)P signaling" @default.
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- W2156421803 doi "https://doi.org/10.1091/mbc.e10-09-0756" @default.
- W2156421803 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3031466" @default.
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